Coordinating respiratory and cardiovascular hemodynamics

ABSTRACT

The present invention is generally directed to methods, systems, and computer program products for coordinating musculoskeletal and cardiovascular hemodynamics. In some embodiments, a heart pacing signal causes heart contractions to occur with an essentially constant time relationship with respect to rhythmic musculoskeletal activity. In other embodiments, prompts (e.g., audio, graphical, etc.) are provided to a user to assist them in timing of their rhythmic musculoskeletal activity relative to timing of their cardiovascular cycle. In further embodiments, accurately indicating a heart condition during a cardiac stress test is increased.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of and priority to U.S. ProvisionalPatent Application Ser. No. 61/798,799, entitled “Systems And MethodsFor Reliably Coordinating Musculoskeletal And CardiovascularHemodynamics”, filed Mar. 15, 2013, which is incorporated herein in itsentirety.

COPYRIGHT NOTICE

A portion of the disclosure of this patent document contains materialthat is subject to copyright protection. The copyright owner has noobjection to the facsimile reproduction by anyone of the patent documentor the patent disclosure as it appears in the Patent and TrademarkOffice patent file or records, but otherwise reserves all copyrightrights whatsoever.

BACKGROUND 1. Field of the Invention

This invention relates generally to the field of human physiology, and,more particularly, to methods, apparatus, systems, and computer programproducts for coordinating musculoskeletal and cardiovascularhemodynamics.

2. Related Art

Blood is circulated through the body by the heart during its rhythmicpumping cycle, which consists of two distinct periods—systole anddiastole. Heart muscle (myocardium) contracts to eject blood from theventricles during the systolic period of each cardiac cycle (CC).Ejection of blood from the ventricles generates arterial blood pressureand flow adequate to deliver blood throughout the body, therebytransporting oxygen, nutrients and metabolic products, removing carbondioxide and waste, and facilitating critical physiological functionssuch as heat exchange. The heart subsequently relaxes during thediastolic period of the CC, when the atrial and ventricular chambersrefill with blood in preparation for the heart's next contraction.

Unlike the rest of the body, which receives most of its blood flow as aresult of pressure generated during systole, the heart's own arterialblood supply is delivered primarily during the diastolic portion of thecycle when the heart muscle is relaxing and the heart chambers arefilling for the next contraction. Little blood flows to perfuse themyocardium during systole because the heart's contraction generates highforces within its muscular walls and thereby prevents flow through thecoronary blood vessels that travel across and through the myocardium.During diastole, when the heart muscle has relaxed, residual bloodpressure in the aorta drives blood flow through the coronary arteriesand into the myocardial muscle, supplying the heart with its neededoxygen and nutrients.

In addition to the heart's pumping function, the musculoskeletal (MSK)system also plays an important role in circulating blood throughout thebody during physical activity. Arterial and venous blood is pumpedrhythmically throughout the body via transient changes in peripheralvascular pressure induced by many types of repetitive MSK activities.Skeletal muscle contraction and relaxation cycles during rhythmicphysical activities cause regular oscillations in peripheral arterialand venous blood pressure or flow due to intermittent compression of thevasculature, while MSK movement can lead to periodic acceleration anddeceleration of the intravascular volume of blood against gravity andinertia.

When rhythmic muscle contractions and MSK movements are favorablycoordinated with the heart's pump cycle, the two pumping systems canaugment one another, thereby increasing blood flow and perfusion toimportant areas of the body with less pumping energy expended by theheart. This favorable coordination of the two pumping systems can bereferred to as “musculoskeletal counterpulsation” (MCP). During MCP,maximum rhythmic MSK-induced blood pumping consistently occurs while theheart is relaxing and refilling between contractions, and the maximumcardiac induced pumping consistently occurs between MSK maximal pumpingevents. On the other hand, when rhythmic muscle contractions and MSKmovements occur with uncoordinated, or worse, unfavorably coordinatedtiming, blood flow and perfusion are decreased along with a concurrentdecrease in pumping efficiencies. Unfavorable coordination occurs, forexample, when the CV and MSK systems consistently pump blood maximallyinto the central circulation at substantially the same time duringrhythmic physical activity. This unfavorable coordination of the twopumping systems can be referred to as “inverse musculoskeletalcounterpulsation” (iMCP).

Typically, when individuals walk, run, bicycle, or participate in anyrhythmic physical activity, most experience favorable coordinationbetween MSK blood pumping and CV blood pumping only occasionally. Evenwhen an individual's heart rate (HR) and exercise cadence happen to beequal, the respective timing of the two pumps may result in favorable orunfavorable coordination, or somewhere in between. Research has shownthat a certain degree of “cardio-locomotor synchronization” can occurduring rhythmic physical activity, in which the timing of anindividual's MSK pump cycle relative to their heart's pump cycle tends,statistically, to naturally favor MCP. However, when such synchrony doesoccur, it is usually only a temporary phenomenon since HR and/or cadencecan change as environmental factors vary (e.g., running in hilly terrainor variable wind), or with any of several physical changes, such asalterations in effort or speed, hydration, temperature, catecholaminelevels or fatigue.

The benefits of favorable coordination between MSK movements and theheart's pump cycle can include improved perfusion and oxygenation ofcardiac and peripheral skeletal muscle and possibly other tissues; alower heart rate (H R) due to increased cardiac preload and strokevolume; a decrease in systolic blood pressure and pulse pressure; adecrease in required respiratory effort to meet the decreased oxygendemands; less muscle fatigue due to improved skeletal muscle perfusion.All of these benefits can combine to result in increased physiologicalefficiency, decreased myocardial stress, increased aerobic energyproduction capabilities and improved potential for aerobic fatmetabolism, enhanced individual performance, and a potential increase inthe health benefits and safety of rhythmic physical activity.Conversely, lack of coordination or unfavorable coordination between MSKmovements and the heart's pump cycle can lead to the opposite of all ofthese effects.

As an individual's level of physical activity increases, the typicalhealthy heart increases its rate of pumping in response to the increasedmetabolic demands generated by the intensity of the action. In somehearts, this chronotropic capability is compromised and the individualsare said to be chronotropically incompetent. As a result, the individualfaces symptoms that include shortness of breath during activities ofmodest intensity, which impairs quality-of-life. Individuals sufferingfrom chronotropic incompetence are typically treated with an implantedrate-responsive pacemaker that stimulates the heart at a ratecommensurate with the intensity of the activity. Pacemakers can usedifferent mechanisms to determine rate responsiveness for a specificintensity of activity. Also, several mechanisms exist to measure theintensity of activity.

The earliest pacemakers were not rate responsive and had only thecapability to provide stimulation pulses to the heart at a fixed cardiacpacing rate. A patient could feel wide-awake when attempting to sleep orexhausted while attempting to exercise because their heart was beatingat a steady rate that might be too high for comfortable resting but toolow to meet the metabolic demands of many levels of physical activity.

To address problems with fixed-rate pacemakers, numerous methods havebeen used to adjust the pacing signals to the heart in response to thepatient's immediate need. Such methods include accelerometry to sensethe level of patient activity; thoracic impedance changes to reflectminute ventilation; temperature measurements as indicators of centralvenous temperature; QT sensors for measuring QT interval variations (ametric on the electrocardiogram/electromyogram). QT sensors are muchbetter metabolic sensors and QT interval variations are a function ofthe intensity of activity and circulating catecholamine in the bloodstream. Consequently, QT sensors are highly specific to exercise andpost-exercise recovery as well as mental stress. Additionally, sensorscapable of measuring physiologic responses, such as changes in bloodpressure, blood oxygen content, pulse rate, blood flow, or myocardial orendocardial tissue acceleration, may also be used in conjunction withany of the above mentioned rate response sensors, to get more specificinformation about intra cardiac activity and to regulate the HR byappropriately timing the stimulating pulse from the pacemaker.

Each of these prior pacemaker rate-adjusting methods comes with theirrespective advantages and limitations. Nonetheless, adapting the pacingrate in response to one or more such sensing modalities offersadvantages over the earlier non-rate responsive devices. None of theseapproaches however has attempted to coordinate the timing of the heart'spump cycle with the patient's repetitive physical activities.

Cardiac exercise stress testing is an important diagnostic modality thattypically tests cardiac function during rhythmic physical activity (e.g.treadmill walking and running, and bicycle exercising). These tests areplagued by frequent false positive results. Uncontrolled rhythmic MSKactivity that matches the patient's HR during the observation period mayinfluence the apparent results, unbeknownst to the clinician performingthe analysis.

BRIEF DESCRIPTION OF THE DRAWINGS

The specific features, aspects and advantages of the present inventionwill become better understood with regard to the following descriptionand accompanying drawings where:

FIG. 1A illustrates a central arterial blood pressure curve for anindividual at rest.

FIG. 1B illustrates a central arterial blood pressure curve for anindividual during physical activity when musculoskeletal (MSK) movementsand the heart's pump cycle are unfavorably coordinated.

FIG. 1C illustrates a central arterial blood pressure curve for anindividual during physical activity when musculoskeletal (MSK) movementsand the heart's pump cycle are favorably coordinated.

FIG. 2 illustrates example timing relationships between an ECG tracing,a central arterial pressure waveform, and skeletal muscle contractioncycles relative to the timing of an example cardiac pacing signal for anindividual.

FIG. 3A illustrates an example architecture for a pacemaker system.

FIG. 3B illustrates an example architecture for a pacemaker system.

FIG. 4 illustrates a flow chart of an example method for coordinatingcardiovascular pump timing with detected musculoskeletal pump timing tofacilitate favorable cardiovascular hemodynamics in an individual.

FIG. 5 illustrates a flow chart of an example method for coordinatingtiming of cardiac pacing to optimize hemodynamics throughmusculoskeletal (MSK) counterpulsation.

FIG. 6 illustrates a flow chart of an example method for coordinatingtiming of cardiac pacing to optimize hemodynamics throughmusculoskeletal (MSK) counterpulsation.

FIG. 7 illustrates a flow chart of an example method for coordinatingtiming of cardiac pacing to optimize hemodynamics throughpacemaker-induced counterpulsation (PC).

FIG. 8 illustrates an example architecture of a multi-sensor dynamicrate responsive pacing system.

FIG. 9 illustrates an example representation of activity sensors andactivity sensor processing circuits.

FIG. 10 illustrates a flow chart of an example method for determiningideal rate response using musculoskeletal (MSK) frequency andmulti-sensor feedback.

FIG. 11 illustrates a flow chart of an example method for guiding a userto obtain favorable coordination of timing between musculoskeletal andcardiovascular pumping.

FIGS. 12A, 12B, and 12C illustrate example user interface screens ofvisual user prompts.

FIGS. 13A and 13B illustrate example user interface screens of visualuser prompts.

FIG. 14 illustrates a flow chart of an example method for changingprompt magnitudes to guide a user to obtain favorable coordination oftiming between musculoskeletal and cardiovascular pumping.

FIG. 15 illustrates an example of a wrist worn device that guides anindividual to optimize the timing of rhythmic musculoskeletal.

FIGS. 16A, 16B, and 16C illustrate example step sequences that can bepresented to an individual when playing a game.

FIG. 17 illustrates a flow chart of an example method for use during anexercise stress test to reduce false positives.

FIG. 18 illustrates an example block diagram of a computing device.

DETAILED DESCRIPTION

The present invention extends to methods, systems, apparatus, andcomputer program products for coordinating musculoskeletal andcardiovascular hemodynamics.

In general, embodiments of the present invention facilitate favorablecoordination of musculoskeletal (MSK) pump timing and cardiac pumptiming. Hemodynamic capacity and cardiac functional capabilities can beimproved during rhythmic MSK activity by maintaining favorablecoordination between the timing of blood pumped by the rhythmic MSKactivity and the timing of a corresponding cardiac pumping cycle. Insome embodiments, favorable coordination includes an individual'sartificial pacemaker providing electrical signals to cause the heart tocontract in proper synchrony with the individual's sensed repetitive MSKactivity. In other embodiments, favorable coordination includes anindividual voluntarily pumping blood via MSK movement or skeletal musclecontraction in proper synchrony with the individual's sensed heart pumptiming. Real-time measurements of an individual's heart pump timing andrhythmic MSK activity timings (e.g., movement or MSK contraction timing)can be used to provide biofeedback or control enabling an individual tomaintain musculoskeletal counterpulsation (MCP) during rhythmic physicalactivity for extended amounts of time.

In “beat to the step” embodiments, MCP is implemented in an automatedfashion using an artificial cardiac pacemaker. A pacemaker can senseboth cardiovascular (CV) and physical activity for an individual. Forexample, a pacemaker can include movement sensors (e.g. pacemakeraccelerometers or other sensors) that sense an individual's rhythmicphysical movements, such as regular movements that occur with ambulationor many forms of exercise. Based on the sensed movement, the pacemakercan adjust the timing of any paced cardiac cycles such that the CV pumpcycle is coordinated with MSK pump cycles so that left ventricularejection occurs at a timing in-between MSK activity-induced bloodpumping events (e.g., foot strikes during ambulation). As such, maximalMSK activity-induced blood pumping occurs during the targeted portion ofcardiac diastole (this can be referred to as pacemaker-inducedcounterpulsation). Pacemaker-induced counterpulsation (PC) benefits anindividual's hemodynamics, including potentially increasing tissueperfusion, while also decreasing systemic vascular resistance, arterialpulse pressure, and the metabolic requirements of the heart.

A cardiac-MSK coordinated pump system can be calibrated to optimallycoordinate the relaxation phase of the cardiac pumping cycle to thetiming of maximal MSK activity-induced blood flow.

In other “step to the beat” embodiments, an individual can be promptedto adjust the timing of MSK activity for coordination with the CV pumpcycle so that left ventricular ejection occurs at a timing in-betweenrhythmic MSK events (e.g., foot strikes during ambulation, pedal pushesduring bicycling, or isometric muscular contractions during upperextremity exercise). In “step to the beat” embodiments, individuals canbe provided with additional guidance (i.e., beyond MSK pump timing), forexample, in helping the individual to coordinate breath timing with MSKactivity (“breathe to the step” or “breathe to the beat”) whilesimultaneously achieving MCP. For example, individuals can be providedwith guidance to breathe at a cadence matching a multiple of theirsteps.

A graphical user interface (GUI) can provide an individual with visualfeedback on the accuracy of achieving MCP. The visual feedback canrelate to the coordination of MSK activity and CV pump cycle. The GUIcan show a cadence graphic along with a HR graphic on the same graphicalscale. As the individual gets closer to matching MSK activity timing andCV pump cycle timing, the cadence graphic and the FIR graphic movecloser to one another. When MSK activity timing and CV pump cycle timingare appropriately matched, the cadence graphic and the HR graphic are ontop of one another. As the individual gets further from matching MSKactivity timing and CV pump cycle timing, the cadence graphic and the HRgraphic move away from to one another.

Other types of GUIs can be integrated into video games, such as, forexample, “Dance Dance Revolution”. An individual can score points for atarget physical action when the timing of the target physical action(e.g., an MSK pump) is in proper sync with the target timing of the beat(pump) of the individual's heart.

Individuals (e.g., athletes) can be weaned from devices that assist withfavorable coordination of MSK pump timing and cardiac pump timing.Algorithms can be used to help individuals feel and recognize the effectof improved blood flow dynamics without assistance from externaldevices.

In other embodiments, the timing of rhythmic physical activity relativeto a monitored Electrocardiogram (ECG) is analyzed during an exercisestress test. The analysis can expose ECG changes potentially (or likely)to be related to effects of inverse musculoskeletal counterpulsation(iMCP), as opposed to some other cardiac condition such as heartdisease, on cardiac stress or perfusion. The analysis can also identifyECG changes that can appear to reflect pathology (e.g. apparent STsegment depression) but also can be readily caused by motion artifactsthat can occur when inertial changes during rhythmic step timing areconsistently aligned with portions or aspects of the heart's cycle (andthat might otherwise be indicated as a false positive for a cardiaccondition, such as, coronary artery disease.)

In general, embodiments of the invention also enable a user to avoid(possibly inadvertent) unfavorable coordination of MSK movement andskeletal muscle contraction cycles with cardiac pumping cycle duringphysical activity.

In the following description of the present invention, reference is madeto the accompanying drawings, which form a part hereof, and in which isshown by way of illustration specific embodiments in which the inventionis may be practiced. It is understood that other embodiments may beutilized and structural changes may be made without departing from thescope of the present invention.

Embodiments of the present invention may comprise or utilize a specialpurpose or general-purpose computer including computer hardware, suchas, for example, one or more processors and system memory, as discussedin greater detail below. Embodiments within the scope of the presentinvention also include physical and other computer-readable media forcarrying or storing computer-executable instructions and/or datastructures. Such computer-readable media can be any available media thatcan be accessed by a general purpose or special purpose computer system.Computer-readable media that store computer-executable instructions arecomputer storage media (devices). Computer-readable media that carrycomputer-executable instructions are transmission media. Thus, by way ofexample, and not limitation, embodiments of the invention can compriseat least two distinctly different kinds of computer-readable media:computer storage media (devices) and transmission media.

Computer storage media (devices) includes RAM, ROM, EEPROM. CD-ROM,solid state drives (“SSDs”) (e.g., based on RAM). Flash memory,phase-change memory (“PCM”), other types of memory, other optical diskstorage, magnetic disk storage or other magnetic storage devices, or anyother medium which can be used to store desired program code means inthe form of computer-executable instructions or data structures andwhich can be accessed by a general purpose or special purpose computer.

A “network” is defined as one or more data links that enable thetransport of electronic data between computer systems and/or modulesand/or other electronic devices. When information is transferred orprovided over a network or another communications connection (eitherhardwired, wireless, or a combination of hardwired or wireless) to acomputer, the computer properly views the connection as a transmissionmedium. Transmissions media can include a network and/or data linkswhich can be used to carry desired program code means in the form ofcomputer-executable instructions or data structures and which can beaccessed by a general purpose or special purpose computer. Combinationsof the above should also be included within the scope ofcomputer-readable media.

Further, upon reaching various computer system components, program codemeans in the form of computer-executable instructions or data structurescan be transferred automatically from transmission media to computerstorage media (devices) (or vice versa). For example,computer-executable instructions or data structures received over anetwork or data link can be buffered in RAM within a network interfacemodule (e.g., a “NIC”), and then eventually transferred to computersystem RAM and/or to less volatile computer storage media (devices) at acomputer system. RAM can also include solid state drives (SSDs or PCIxbased real time memory tiered Storage, such as FusionIO). Thus, itshould be understood that computer storage media (devices) can beincluded in computer system components that also (or even primarily)utilize transmission media.

Computer-executable instructions comprise, for example, instructions anddata which, when executed at a processor, cause a general purposecomputer, special purpose computer, or special purpose processing deviceto perform a certain function or group of functions. The computerexecutable instructions may be, for example, binaries, intermediateformat instructions such as assembly language, or even source code.Although the subject matter has been described in language specific tostructural features and/or methodological acts, it is to be understoodthat the subject matter defined in the appended claims is notnecessarily limited to the described features or acts described above.Rather, the described features and acts are disclosed as example formsof implementing the claims.

Those skilled in the art will appreciate that the invention may bepracticed in network computing environments with many types of computersystem configurations, including, personal computers, desktop computers,laptop computers, message processors, hand-held devices, multi-processorsystems, microprocessor-based or programmable consumer electronics(including wearable electronics, such as, wristbands and ear pieces),pacemakers, fitness equipment (e.g., treadmills) network PCs, gameconsoles, minicomputers, mainframe computers, mobile telephones, PDAs,tablets, pagers, routers, switches, various storage devices, and thelike. The invention may also be practiced in distributed systemenvironments where local and remote computer systems, which are linked(either by hardwired data links, wireless data links, or by acombination of hardwired and wireless data links) through a network,both perform tasks. In a distributed system environment, program modulesmay be located in both local and remote memory storage devices.

Embodiments of the invention can also be implemented in cloud computingenvironments. In this description and the following claims, “cloudcomputing” is defined as a model for enabling ubiquitous, convenient,on-demand network access to a shared pool of configurable computingresources (e.g., networks, servers, storage, applications, and services)that can be rapidly provisioned via virtualization and released withminimal management effort or service provider interaction, and thenscaled accordingly. A cloud model can be composed of variouscharacteristics (e.g., on-demand self-service, broad network access,resource pooling, rapid elasticity, measured service, etc.), servicemodels (e.g., Software as a Service (SaaS), Platform as a Service(PaaS), Infrastructure as a Service (IaaS), and deployment models (e.g.,private cloud, community cloud, public cloud, hybrid cloud, etc.).Databases and servers described with respect to the present inventioncan be included in a cloud model.

Further, where appropriate, functions described herein can be performedin one or more of: hardware, software, firmware, digital components, oranalog components. For example, one or more application specificintegrated circuits (ASICs) can be programmed to carry out one or moreof the systems and procedures described herein. Certain terms are usedthroughout the following description and Claims to refer to particularsystem components. As one skilled in the art will appreciate, componentsmay be referred to by different names. This document does not intend todistinguish between components that differ in name, but not function.

For the purpose of clarity, the following terminology and abbreviationsare used throughout this description and following claims:

-   -   CC Cardiac Cycle, equivalently Cardiovascular Cycle    -   CV Cardiovascular    -   ECG Electrocardiogram    -   ECP External Counterpulsation    -   EMG Electromyogram    -   HR Heart Rate    -   iMCP Inverse Musculoskeletal Counterpulsation    -   MCP Musculoskeletal Counterpulsation    -   MSK Musculoskeletal    -   PC Pacemaker-Induced Counterpulsation    -   RRI R-wave to R-wave interval (R-R time interval) within an ECG        signal

In this application, “MSK activity” and “MSK pumping” includes at leastone of muscle contraction and MSK movement and their related inertialand pumping effects on blood pressure and blood flow. In addition, theterms “cardiac pumping” and “cardiovascular pumping” are usedinterchangeably.

In general, hemodynamic effects of musculoskeletal counterpulsation(MCP) can be illustrated by comparing an example central arterial bloodpressure curve of an individual at rest to example central arterialblood pressure curves of the same individual during physical activity.FIG. 1A depicts a graph 101 of a central arterial blood pressure curvefor a typical healthy young elastic aorta when the individual is atrest. Graph 101 depicts systolic pressure wave 10 during cardiac systole11. Systolic pressure wave 10 ends and diastolic pressure wave 14 beginsat aortic valve closure (dicrotic notch 12). Graph 101 depicts diastolicpressure wave 14 during cardiac diastole 13.

FIG. 1B depicts a graph 102 of an example of a central arterial bloodpressure curve in the same individual during physical activity when MSKmovements and the heart's pump cycle arc unfavorably coordinated, asoccurs with iMCP. That is, when maximal pumping of blood towards theheart by the MSK system occurs at the same time as cardiac systole 11(heart pumping blood to into the aorta). This unfavorable conditioncauses the cardiac and MSK pumping mechanisms to temporarily directlyoppose the action of one another, as the two pumps simultaneously pushblood in opposite directions, towards one another, within the samecentral arteries. This can lead to multiple undesirable effects,including any or all of: decreased pumping efficiency, increasedsystolic blood pressure (e.g., as indicated by systolic pressure wave16), increased HR, increased myocardial energy demand, decreasedarterial perfusion, decreased muscle perfusion, and earlier fatigue.Each of these undesirable effects can lead to increases in health risk,particularly in extreme or at risk circumstances, due to the possibilityof inadequate myocardial perfusion concurrent with an increasedmyocardial work load. The detrimental effect can be made worse when theunfavorably coordinated pumping results in lower central arterial andvenous pressure during diastole (e.g., as indicated by diastolicpressure wave 19), potentially decreasing both myocardial perfusion andfilling of the hearts pumping chambers.

Conversely, FIG. 1C depicts a graph 103 of an example of a centralarterial blood pressure curve in the same individual during physicalactivity when MSK movements and the heart's pump cycle are favorablycoordinated, as occurs with MCP. That is, when maximal relaxation of theMSK system is during cardiac systole 11 and when maximal pumping ofblood towards the heart by the MSK system is during cardiac diastole 11(i.e., the heart at rest refilling with blood). Maximal relaxation ofthe MSK system during cardiac systole 11 decreases systolic centralblood pressure (e.g., as indicated by systolic pressure wave 18). On theother hand, maximal pumping of blood towards the heart by the MSK systemduring cardiac diastole 13 increases diastolic central blood pressure(e.g., as indicated by diastolic pressure wave 20).

As individuals age, the aorta loses its elasticity, leading to a classicincrease in baseline systolic blood pressure, since the heart is pumpingblood into a stiffer tube (aorta). Loss of aortic elasticity also leadsto a decrease in diastolic blood pressure, because the stiff aorta isless able to maintain pressure without the heart actively generatingpressure, as it does during systole. Thus, graph 102 can also representcharacteristics of a central arterial (e.g., aortic) waveform that onemight expect to see in an elderly individual at rest and is contrary toa healthy young individual at rest, as depicted in graph 101.

FIG. 2 illustrates example timing relationships between an ECG tracing22, central arterial pressure waveform 32, skeletal muscle contractioncycles 36 and 37, and the timing of an example cardiac pacing signal 34for an individual. ECG tracing 22 depicts various different wavesincluding P-waves, Q-waves, R-waves, S-waves, and T-waves.

R-waves 24 (including 24 a, 24 b, and 24 c) represent depolarization ofthe myocardium of the ventricular walls of the heart. R-waves 24 can beutilized in the measurement of HR via the measurement of the duration ofR-to-R intervals (RRI) 26. RRIs 26 can vary beat-to-beat and measurementof that variation is called heart rate variability (HRV). T-wave portion28 reflects ventricular repolarization. T-wave end 30 can be used as amarker of the approximate timing of aortic valve closure during theheart's pumping cycle. T-wave end 30 and aortic valve closure also bothoccur with timing that corresponds to dicrotic notch 12 of a centralarterial pressure wave.

Examples of targeted MSK timing 36 and 37 both include brief periods ofskeletal muscle contraction during cardiac diastole 13 followed byperiods of relaxation. MSK events 35 identify a period in time thatcorresponds to, for example, the onset of activity-related musclecontractions. In targeted MSK timing 36, the muscle contractions aretimed by the user to begin at prompts corresponding to MSK events 35that repeat, in this example, with each instance of the Cardiac Cycle(CC). That is MSK:CC=1:1. In targeted MSK timing 37, the prompts andmuscle contractions repeat with every other CC. That is MSK:CC=1:2. Theuser can opt or be directed to initiate an MSK event with each prompt,or multiple times per prompt (e.g. prompt corresponds to every otherfoot strike during running).

As depicted, pacer timing signal 34 (e.g., for timing a correspondingpacemaker) includes delay time 39. Delay time 39 indicates theequivalent MSK event 35-to-R-wave 24 relationship for initiating thedepolarization of the ventricles artificially to favorably coordinateMSK and heart pumps. (Pacer timing signal 34, in this example, maycorrespond most closely to Ventricular Pacing; alterative pacing signalcharacteristics are also contemplated (e.g., Atrial, AV synchronous, andBiventricular Pacing), each of which would require a different delaytime 39 to achieve the equivalent MSK event 35 to cardiac musclecontraction timing relationship.)

Scale 38 represented the percent of the RRI 26 nomenclature used herein.For example, 0% and 100% represent events timed coincident with theR-waves 24, while 25% of the RRI is a quarter of the way betweensuccessive R-waves 24 (e.g., between 24 b and 24 c), and 50% is themid-point between R-waves 24. Scale 38 can alternatively be expressedfractionally as a value from zero to one, in units of degrees betweenzero and 360 degrees, or in radians between zero and 2π radians (e.g.,25%=0.25=90 degrees=1.57 radians), equivalent to the percentageterminology. Values greater than 100% describe events in a subsequentR-R interval (e.g., 130% represents a 30% location in the followinginterval).

Coordinating CV Pumping with MSK Pumping Through EketronicCardiac Pacing

In this description and the following claims, the terms pacemaker,artificial pacemaker, electronic pacemaker and extrinsic pacemaker areused interchangeably to describe artificial heart pacing devicescommonly provided in a patient whose heart's natural intrinsicpacemakers are not functioning properly, or when cardiacresynchronization therapy can otherwise potentially improve quality oflife in the face of impaired cardiac function.

Embodiments of the invention enable an artificial pacemaker, or otherimplantable system, such as a single chamber, dual chamber, orbiventricular pacemaker supporting a patient with a heart conditions(e.g., symptomatic bradycardia, chronotropic incompetence, heart block,congestive heart failure, etc.) to operate in favorable synchrony with asensed rhythmic MSK activity in a patient. Favorable synchrony includesthe relaxation phase of the cardiac pumping cycle (diastole) and thetiming of maximal central blood pumping via MSK movement and skeletalmuscle contraction (e.g. foot strike while walking) substantiallyaligning. Favorable synchrony also includes the contraction phase of thecardiac pumping cycle (systole) and the timing of maximal skeletalmuscle relaxation substantially aligning, thereby optimizing muscleperfusion and blood pressures during those activities. Numerous patientsrequiring cardiac rhythm management have severely compromised cardiacfunction and any modest increase in cardiac perfusion can significantlyincrease cardiac contractility leading to better hemodynamics for thepatient.

In general, a cardiac-MSK coordination system can determine a targetheart pump timing using single or multiple sensors responsive to patientactivity, and then use this timing information when creatingheart-pacing signals.

FIG. 3A illustrates an example architecture 300 for implantablepacemaker system 301. As depicted, implantable pacemaker system 301includes activity sensor(s) 302, processor (or other controller) 303,ECG sensor 304, pulse generator 306, one or more electrical lead(s) 307.Electrical lead(s) 307 connect implantable pacemaker system 301 to heart321. Lead(s) 307 can be of any standard length including, for example,very short prongs that comprises the leads of what are referred to as“leadless pacemakers”. All or a portion of pacemaker system 301 can beimplanted in individual 322 to assist with pumping individual 322'sheart 321. Embodiments of this system 301 can include an implantablecardio-defibrillator (ICD) along with the pacemaker. Implantablepacemaker system 301 can also include other affiliated components (notshown), such as, for example, additional physiological sensor(s), abattery, etc.

Activity sensor(s) 302 can be built into pacemaker system 301 (or adefibrillator). Activity sensor(s) 302 can include one or more of avariety of different components including but not limited to: uniaxialand multiaxial accelerometers, magnetometers, gyroscopes, piezoelectricmaterials, pressure sensors, and other motion/activity sensors that areresponsive to MSK activity in an individual. Accelerometers can be3-axis sensors and can be packaged with gyroscopes, magnetometers,temperature monitors and other sensors. As such, embodiments includingaccelerometers may inherently include any of these other type ofsensors. Further, any combination of commonly used and availableinternal or external activity sensors that are capable of reliablymeasuring rhythmic MSK activity can provide the activity sensingfunction of the pacemaker device, thereby enabling PC through thefavorable coordination of MSK pump timing and cardiac pump timing.

Activity sensor(s) 302 can be co-located within implantable pacemakersystem 301 or within a lead or otherwise integrated form factors in linewith implantable pacemaker system 301. Generally, activity sensor(s) 302sense(s) and interpret(s) sensor signals in order to detect andcharacterize movement and its timing during rhythmic physicalactivities, including but not limited to walking, running, swimming,climbing, rowing, etc. Signals from activity sensor(s) 302 can be sentto processor 303. Alternatively, the processing for detecting,characterizing movement and its timing from activity sensor(s) 302signals may be performed by processor 303 without departing from theconcepts described herein.

ECG sensor 304 is configured to monitor and interpret electricalactivity of heart 321 over a period of time as detected via leads 307(e.g., as represented by EGC signal 22 in FIG. 2). ECG sensor 304 withleads(s) 307 (or other conduction technology) can be used to sensenatural depolarization of the heart, minute ventilation via impedance,and contractility of myocardium using bipolar leads. Signals (indicatingthese and other types of measurements) from ECG sensor 304 can be sentto processor 303. In some embodiments, a baseline (lower frequency)component of an ECG signal is sensed and used to determine repetitivemovement. In further embodiments, pacemaker system 301 can include or beintegrated with additional internal physiological sensors (not shown),for example, sensors that measure arterial or cardiac pressures, pH,glucose, lactate, cardiac enzymes, or blood gas concentrations.

The available real-time physiological measurements can be used inalgorithms to measure and control optimal hemodynamics. For example, anautomated calibration algorithm can be programmed to enable the systemto determine the optimal relative timing for CV pump vs. MSK pump bypacing the heart such that ventricular contraction is systematicallytriggered at different timing locations during a rhythmic MSK pumpingcycle, while the individual's physiological response is measured viaphysiological sensors. Measures that change in correlation with relativeCV vs. MSK pump timing, for example fluctuations in contractility, bloodpressure, cardiac output, tissue oxygenation, tissue pH and minutevolume, can then be used to identity optimal target CV pump vs. MSK pumptimings.

Processor 303 is configured with signal processing capabilities.Processor 303 can receive signals from activity sensor(s) 302 and/or ECGsensor 304. The signal processing capabilities can process receivedsignals to identity refined motion elements, such as, impact andorientation from ground reaction forces (e.g., heel strike, loadingresponse, etc.) and derive metrics, such as, stride frequency (cadence),maximal muscle contraction timing, timing or magnitude of rhythmicchanges in inertia, precise step timing, changes in elevation, durationof foot-ground contact time, foot strike ergonomics, balance, etc. Basedon identified refined motion elements and/or derived metrics, processor303 can interoperate with pulse generator 306 to control the timing ofstimulating heart 321 (e.g., to favorably coordinate CV pump timing withdetected MSK pump timing).

Pulse generator 306 and lead(s) 307 are configured to processinformation and electrically stimulate cardiac myocytes above adepolarization threshold. Electrical stimulation above thedepolarization threshold activates the conduction system of the heartand causes cardiac systole. Placement of lead(s) 307 (e.g. right atrium,one or both ventricles) depends on the pacemaker functionality desired(e.g. atrial, ventricular, AV synchronized, or biventricular pacing).

Pulse generator 306 (or other additional pacemaker system components)can also include built-in rate-responsive pacing circuitry thatgenerates stimulation pulses on demand at a rate and timing determinedat least in pan by the frequency and timing of the repetitive MSKactivity. Target timing of the stimulation pulses during certainrhythmic physical activities can be determined by computing a timingvalue based on a function of the sensed MSK pump timing.

Implantable pacemaker systems are not limited to internal activitysensors. Implantable pacemaker systems can utilize other (external)independent physiologic sensors or a combination of physiologic sensors,such as, for example, respiratory, cardiac function, motion, force,temperature, EMG, ECG, electroencephalogram, photoplethysmogram, orother sensors responsive to body motions. These other sensors canfurther characterize drivers of MSK pumping, including the force ofskeletal muscle contraction and relaxation, and inertial changes thatoccur with body movement as well as to reveal the impact of MSK pumptiming on other organ systems.

For example, FIG. 3B illustrates an example architecture 310 forimplantable pacemaker system 311. As depicted, implantable pacemakersystem 311 includes receiver 313, processor (or other controller) 303,ECG sensor 304, pulse generator 306, and electrical lead(s) 307.Electrical lead(s) 307 connect implantable pacemaker system 311 to heart321. Pacemaker system 311 can be implanted in individual 322 to assistwith pumping individual 322's heart 321.

Also depicted are external wireless sensor(s) 312. External wirelesssensor(s) 312 is external to (e.g., not implanted inside of) anindividual. External wireless sensor(s) 312 can include one or more ofany of the described MSK activity sensors and one or more of the otherdescribed implanted or external physiological measurement sensors.External wireless sensor(s) 312 can also include wireless communicationcapabilities for communicating with receiver 313. Similarly, receiver313 can include wireless communication capabilities for communicatingwith external wireless sensor(s) 312.

Generally, external wireless sensor(s) 312 sense(s) and interpret(s)sensor signals in order to detect and characterize movement and its timeduring rhythmic physical activities, including but not limited towalking, running, swimming, climbing, rowing, etc., or the physiologicaleffect of rhythmic MSK activity timing relative to CV pump timing.Signals from external wireless sensor(s) 312 can be sent via wirelesscommunication to receiver 313. Receiver 313 can receive signals viawireless communication from external wireless sensor(s) 312. Receiver313 can forward signals from external wireless sensor(s) 312 toprocessor 303. Processing of signals from external wireless sensor(s)312 to derive relevant information (such as MSK event timing 35) can beaccomplished within an external wireless sensor 312, or withinprocessor/controller 303, without departing from the concepts describedherein.

The other components of pacemaker system 311 operate similarly to likenumbered components of pacemaker system 301.

As such, an activity sensor can be an externally worn device or animplanted (and possibly pacemaker integrated) device that communicatesvia wired or wireless transmission with processor 303 and pulsegenerator 306. In some embodiments, a pacemaker system includes bothimplanted sensor(s) (e.g., activity sensor(s) 302, other physiologicalsensors) and external sensors (e.g., external wireless sensor(s) 312)and receiving mechanisms (e.g., receiver 313). In these embodiments,processor 303 and pulse generator can receive and process signals fromboth internal and external sensors.

Accordingly, utilizing the described (and other) components, a pacemakersystem can facilitate measurement of MSK activity and depolarize theheart at the proper time to optimize hemodynamics. Similar functionalitycan be merged with conventional pacing applications used for therapeuticpurposes (e.g., treating arrhythmia, bradycardia, chronotropicincompetence, etc.) by adjusting the specific timing of those pacingsignals to properly coordinate the heart pump timing with the sensed MSKactivity; or, if more generally indicated, by coordinated timed pacingof the heart with the MSK events whenever persistent rhythmic movementis detected and, for example, HR and cadence are sufficiently similarand/or meet specified conditions.

FIG. 4 illustrates a flow chart of an example method 400 forcoordinating cardiovascular pump timing with detected musculoskeletalpump timing to facilitate favorable cardiovascular hemodynamics in anindividual. Method 400 will be described with respect to the componentsof architectures 300 and 310.

Method 400 includes accessing ongoing signals from each of one or moremusculoskeletal activity sensors in a pacemaker (401). For example,processor 303 can access a signal from one or more sensors in activitysensor(s) 302 and/or from one or more sensors in external wirelesssensor(s) 312 and/or from ECG sensor 304.

Method 400 includes processing the accessed signals from each of the oneor more sensors to detect that the individual is engaged in a rhythmicphysical activity, the rhythmic activity having an associatedmusculoskeletal pump timing (402). For example, processor 303 canprocess an accessed signal from one or more sensors in activitysensor(s) 302 and/or from one or more sensors in external wirelesssensor(s) 312 and/or from ECG sensor 304 to determine that individual322 (which pacemaker system 301 or 311 can be implanted in) is engagedin rhythmic physical activity. The rhythmic physical activity individual322 is engaged in can have an associated MSK pump timing.

Method 400 includes determining a target cardiovascular pump timing forthe individual to achieve favorable cardiovascular hemodynamics duringthe rhythmic physical activity (403). For example, processor 303 candetermine an adjustment to CV pump timing for heart 321 to favorablycoordinate the CV pump timing of heart 321 with the MSK pump timingassociated with the rhythmic physical activity individual 322 is engagedin.

Method 400 includes providing a pacing signal to the heart pacing theheart of the individual at the target cardiovascular pump timing for theindividual to favorably coordinate the cardiovascular pump timing withthe associated musculoskeletal pump timing (404). For example, pulsegenerator 106 can implement the determined adjustment to CV pump timingfor heart 321 to facilitate counterpulsation within individual 322 whileindividual 322 is engaged in the rhythmic physical activity. That is,pulse generator 106 can implement an adjustment to CV pump timing forheart 321 to facilitate a central arterial blood pressure curve forindividual 322 that is similar to that of FIG. 1C.

Other mechanisms for improving hemodynamics within an individual arealso contemplated. Some mechanisms calculate rhythmic MSK events andcadence using one or more activity sensors and then electricallystimulate the contraction of the heart to occur at a target timingrelative to the previous or next anticipated MSK event. For example,FIG. 5 illustrates a flow chart of an example method 500 forcoordinating timing of cardiac pacing to optimize hemodynamics throughMSK counterpulsation. Method 500 will be described with respect to thecomponents of architectures 300 and 310.

Method 500 includes sensing the timing of a recurrent MSK event (501).For example, one or more sensors in activity sensor(s) 302 and/or one ormore sensors in external wireless sensors(s) 312 can interoperate withprocessor 303 to sense the timing of a rhythmic MSK event for individual322. Method 500 includes triggering a cardiac pacer at a computed timeafter the recurrent musculoskeletal event (502). For example, processor303 and pulse generator 306 can interoperate to trigger depolarizationof heart 321 at a computed time after the regularly recurring MSK eventfor individual 322.

Algorithms and sensors can be utilized to identify instances when pacingthe heart at a rate that approximates the cadence of the rhythmicphysical activity would be appropriate for the level of exertion. Inthose instances, an electrical pacing system utilizes further timingalgorithms and signals from MSK activity sensors to identify the timingwhen a pacemaker's electrical stimulation results in left ventriculardepolarization timing that is coordinated to the MSK activity cycletiming such that MCP is optimized (i.e., PC).

In some embodiments, an accelerometer is used to detect MSK activity.Additional embodiments include accelerometers along with other movementsensors, for example, gyroscopes and magnetometers, which are frequentlypackaged together and can add further resolution to movement sensing.FIG. 6 illustrates a flow chart of an example method 600 forcoordinating timing of cardiac pacing to optimize hemodynamics throughMSK counterpulsation. Method 600 will be described with respect to thecomponents of architectures 300 and 310.

Method 600 includes sensing an accelerometer signal (601). For example,processor 303 can sense an accelerometer signal from an accelerometer inone of activity sensor(s) 302 or external wireless sensor(s) 312. Method600 includes determining the timing of a recurrent MSK activity from thesensed accelerometer signal (602). For example, processor 303 candetermine the timing (e.g., corresponding, for example, to MSK event 35)of a recurrent MSK activity for individual 322 from the signal sensedfrom the accelerometer in one of activity sensor(s) 302 or in externalwireless sensor(s) 312.

Method 600 includes determining a delay time (e.g., delay 39) after thetiming of a recurrent MSK activity for cardiac pacer trigger (603). Forexample, processor 303 can determine a delay time after the timing ofthe recurrent MSK activity for individual 322 for triggering heart 321.Method 600 includes triggering the cardiac pacer at the determined delaytime (604). For example, processor 303 and pulse generator 306 caninteroperate to trigger a pulse to heart 321 at the determined delaytime after the timing of the recurrent MSK event for individual 322.

In some embodiments, a heart can be electrically stimulated so as toinitiate a cardiac contraction at a precise phase or timing locationwithin a MSK cycle or a time delay relative to a recurrent MSK cycleevent. The cardiac electrical stimulation trigger may be based on apercent of the step-to step-interval; a fixed time delay relative to anidentified recurrent event in the MSK cycle; or a calculated timingbased on at least one of physiologic, historical, test results (e.g.,calibration based) and demographic data after the MSK event or prior toa predicted next MSK event. The timing can be optimized such that thecardiac cycle reaches diastole just as the next predicted MSK pumpingevent occurs. For MSK activity that repeats with a generally stablerhythm or period, the electrical stimulation can be similarly inducedaccording to the same rate and rhythm, phase shifted properly to achievethe hemodynamic effects of PC.

Such properly synchronized behaviors may create some of the hemodynamiceffects and benefits seen with external counterpulsation (ECP) andintra-aortic balloon pump (IABP) devices. Furthermore, as with ECP andIABPs, favorable episodes of counterpulsation may occur when the cardiacrate is an integer multiple of the rhythmic MSK activity rate (i.e.,HR:MSK rate=1:1, 2:1, 3:1, 4:1, etc.), as the timing relationshipremains approximately constant relative to the particular marker of theCCs in which the MSK activity occurs, or vice versa.

FIG. 7 illustrates a flow chart of an example method 700 forcoordinating timing of cardiac pacing to optimize hemodynamics throughPC. Method 700 will be described with respect to the components ofarchitectures 300 and 310.

Method 700 includes sensing an activity sensor signal (701). Forexample, processor 303 can sense an accelerometer signal from anaccelerometer in one of activity sensor(s) 302 or external wirelesssensor(s) 312. Method 700 includes determining if the activity sensorsignal represents rhythmic activity (702). For example, processor 303can determine if the accelerometer signal from the accelerometer in oneof activity sensor(s) 302 or external wireless sensor(s) 312 representsthat individual 322 is engaged in rhythmic MSK activity, for example,ambulation.

Method 700 includes determining continuously or intermittently thedifference between the MSK activity rate and the HR (703). For example,processor 303 can determine the difference between a rhythmic MSKactivity rate that individual 322 is performing and the HR (or thetarget HR range appropriate for the sensed rhythmic physical activity)of heart 321. Method 700 includes determining if the activity rate andthe HR (or the target HR range appropriate for the sensed rhythmic MSKactivity) is sufficiently similar (decision block 704). For example,processor 303 can determine if the activity rate of individual 322 andthe HR (or the target HR range appropriate for the sensed rhythmicphysical activity) of heart 321 are sufficiently similar. If theactivity rate and HR (or the target HR range appropriate for the sensedrhythmic physical activity) are not sufficiently similar (NO at 704),method 700 returns to 701. If the activity rate and HR (or the target HRrange appropriate for the sensed rhythmic physical activity) aresufficiently similar (YES at 704), method 700 proceeds to 705.

Method 700 includes triggering a cardiac pacer with a targeting time (orequivalently, phase) relationship with respect to MSK activity timing(705). For example, processor 303 and pulse generator 306 caninteroperate to trigger pulses to heart 321 at targeted times based onthe timing of MSK activity for individual 322.

A variety of different triggers can be used to initiate PC, includingbut not limited to, increased metabolic demands as identified by minuteventilation and/or the activity sensor, a sensed cyclical MSK activityrhythm detected by the activity sensor, pre-programmed activation duringcertain times of the day, or triggered via an external device such as auser handheld activator.

In some embodiments, PC may also be provided with triggers to not startor turn itself off. For example, a pacemaker system may be programmed tonot enter a PC mode during certain times of the day, or provided withminimum or maximum heart rates, etc. If natural electrical conduction ofthe heart is present, PC may be used to override the natural conduction(one time or ongoing) or may be programmed to turn off if naturalconduction is sensed. Further, internal sensors, such as activity orother physiological sensors incorporated in the pacemaker system 301, orexternal wireless sensor(s) 312, such as those incorporated in thepacemaker system 311, can be programmed to provide information to thesystem that might lead to modification or cancellation of a PC mode. Forexample, internal vascular or cardiac pressure sensors, internalmetabolic sensors, or external EEG sensors can each contribute data to apreprogrammed set of use parameters.

A closed-loop feedback system can be used to further optimize whenelectrical stimulation is triggered. Outputs measured by the implantablesystem, for example minute ventilation, contractility, blood pressure,or intrinsic HR, could be used to adjust and test different phases ofelectrical stimulation during detected MSK activity.

As described embodiments of the invention can include multi-sensorsystems. FIG. 8 illustrates an example of a multi-sensor dynamic rateresponsive pacing system 800. The components of multi-sensor dynamicrate responsive pacing system 800 can be integrated into either ofpacemaker systems 300 and 310 to coordinate rhythmic MSK pump timingwith HR pump timing. As depicted, system 800 includes activity sensor(s)801, minute ventilation sensor(s), and physiologic sensor(s) 803. One ofmore of activity sensor(s) 801, minute ventilation sensor(s), andphysiologic sensor(s) 803 can be implanted in an individual and possiblyintegrated into a pace maker. Sensor processing circuits 811, 812, and813 are configured to process signals from activity sensor(s) 801,minute ventilation sensor(s), and physiologic sensor(s) 803respectively.

Output from each of sensor processing circuits 811, 812, and 813 can besent to logic circuits 814. Logic circuits 814 (e.g., included inprocessor 303) can receive output from each of sensor processingcircuits 811, 812, and 813. From the outputs, logic circuits 814 candetermine a dynamic rate response and assess parameters that dictate theinitiation, termination, calculation, or optimization of PC. Logiccircuits 814 can send the dynamic rate response to pacing stimulationcircuits 816 (e.g., included in pulse generator 306). Pacing stimulationcircuits 816 can receive the dynamic rate response and PC from logiccircuits 814. Logic circuits 814 can used pacing leads 817 to stimulatethe heart in accordance with the dynamic rate response.

FIG. 9 illustrates an example representation 900 of activity sensors andactivity sensor processing circuits. The activity sensors and activitysensor processing circuits in representation 900 can be integrated intoeither of pacemaker systems 300 and 310 to coordinate rhythmic MSK pumptiming with HR pump timing. As depicted, representation 900 includesactivity sensors 901 and activity sensor processing circuits 902.Activity sensors 901 can sense various different types of activity.Activity sensors 901 can indicate the different types of activity toactivity sensor processing circuits 902. Activity sensor processingcircuits 902 can further process data sensed by activity sensors 901 toderive various conclusions about senses activities. The conclusions canbe passed to logic circuits for use in determining a dynamic rateresponse.

For many individuals, dependent to some extent on age, fitness level,and baseline cardiac function, natural cadences during walking andrunning often correlate with natural heart rates during those sameactivities. In fact, this natural correlation may be evolutionarilyderived as the human body adapted towards an inherent capability fornatural cardiolocomotor synchronization and the benefits derived fromnaturally occurring MCP. Therefore, embodiments of the rate responsivesystem are designed to be programmed to leverage the cadence of theindividual during ambulation in order to identify a target paced HR,where HR=Cadence, and where the MSK pump timing at that cadencedetermines the cardiac stimulation timing in order to optimize PC.

FIG. 10 illustrates a flow chart 1000 of an example method fordetermining ideal rate response using MSK frequency and multi-sensorfeedback. Method 1000 can be implemented in pacemaker system 300 or 301including any of the components and functionality included in FIGS. 8and 9.

Method 1000 includes determining if sensed activity exceeds apre-determined threshold (1001). If so, method 1000 includes determiningif the activity is continuous (decision block 1002). If the activity isnot continuous (NO at decision block 1002), method 1000 returns to 1001.If the activity is continuous (YES at decision block 1002), method 1000includes determining if the activity is a repetitive motion (decisionblock 1003)

If the activity is not a repetitive motion (NO at decision block 1003),method 1000 includes utilizing a conventional activity based rateadaptive algorithm (1004). If the activity is a repetitive motion (YESat decision block 1003) or after utilizing a conventional activity basedrate adaptive algorithm, method 1000 includes extracting one or moreparameters from a repetitive motion signal and determining an MSKfrequency rate (1005).

Method 1000 includes determining if intrinsic HR is less than or equalto ideal HR response rate range (decision block 1007). If intrinsic HRis less than or equal to ideal HR response rate range (YES at decisionblock 1007), method 1000 includes watching and delivering stimulation atthe determined MSK frequency rate and preferred timing relative to MSKpump timing to optimize PC. If intrinsic HR is not less than or equal toideal HR response rate range (No at decision block 1007), method 1000includes continuing to monitor HR and cadence of MSK activity.

Individuals can be provided with guidance to assist the individuals inmaintaining a regular cadence or specific cadence. External devices(e.g., activity sensors(s)/transmitter(s) 312, mobile phones, etc.) canprovide guidance through auditory, visual, tactile, or electrical meansof instructing or prompting the user when to step (or perform some otherrhythmic activity) to facilitate PC. Guidance may further encourage theuser to step or otherwise activate their MSK system in ways or at ratesthat enable PC. An external device can receive or transmit data to animplantable pacemaker system to further coordinate counterpulsation.Other external devices, such as accelerometers, may be worn on the userand telemeter information to the pacemaker system to further increasesystem accuracy.

Calibrating a rate-responsive pacing system, either during the implantprocedure or during subsequent physician follow-up visit, or in anautomated fashion during normal physical activity might be warranted tooptimally coordinate the relaxation phase of the cardiac pumping cycleto the timing of maximal MSK movement-induced blood flow. Calibrationcan be repeated in order to accommodate physiological changes over time,for example, optimal timing might require adjustment for changes inbaseline myocardial function, such as, for example, changes related toage-dependent hardening of the vasculature, valvular disease, coronaryartery disease, fluid status (e.g., hydration), hematocrit, leftventricular ejection fraction or myocardial contractility.

A static calibration technique could be performed initially duringimplant and with subsequent follow-up, for example, in order to analyzecentral arterial stiffness and pulse transit time, and accordinglyadjust the delay calculations between pulse wavefront from the heart andthe pulse wavefront from the MSK pump. Alternatively, more sophisticatedsensor-based implementations can be leveraged to dynamically calibratethe co-ordination. Such a calibration step might include a treadmilltest, wherein the patient is monitored for physiological changes duringslightly different step timings relative to the cardiac contractioncycle. Exemplary changes that might be useful in determining optimal CPtiming include variations in respiration or standard respiratorymeasures of energy metabolism (e.g. minute volume. VO2, VCO2, RER):standard measures of cardiac function (e.g. cardiac output, strokevolume, ejection fraction, contractility); tissue oxygenation (e.g.pulse oximetry), tissue or blood measures (e.g., pH, lactate, troponin)or blood pressure.

Accordingly, various embodiments of the invention facilitate thepossibility of improved stamina, oxygen delivery, blood pressure, heartrate variability (marker of physical stress and health), vitality, andhealth benefits. Embodiments have potential application intherapeutically treating myocardial ischemia, heart failure, coronaryartery disease, and other CV and circulatory issues, as well as symptomsof those diseases including angina, shortness of breath, dyspnea onexertion, arrhythmia, and premature fatigue in patients that haveextrinsic cardiac pacing such as with implantable pacemakers andcombination pacemaker/defibrillators.

Coordinating MSK and CV Pumping Through User Prompts (Biofeedback)

Embodiments of the invention include mechanisms for providing real-timefeedback to users. The real-time feedback can help a user to voluntarilyadjust or maintain the timing of their MSK activity and skeletal musclecontractions towards a target timing relationship relative to the timingof their CV pumping cycle in order to obtain and/or maintainsubstantially optimized hemodynamics, for example, to achieve MCP, or toachieve another targeted relationship. Real-time feedback can include arecurring guidance prompt. The guidance prompt can be adaptivelyresponsive to actual relative MSK and CV pump timing or respectiverates, and/or accuracy in achieving the target timing relationship, ormaintaining this condition.

FIG. 11 illustrates a flow chart of an example method 1100 for guiding auser to obtain favorable coordination of timing between musculoskeletaland cardiovascular pumping. Method 1100 includes sensing acardiovascular cycle for individual (1101). For example, one or moresensors, such as, an ECG, a Photoplethysmogram, or an electronicauscultation sensor can be used to sense a cardiovascular cycle for anindividual. The sensor(s) can be included in a device implanted in theindividual (e.g., a physiological monitoring system, a drug deliverysystem, or a pacemaker system 301 or 311) or worn externally by theindividual.

Method 1100 includes providing feedback prompts coordinated with thecardiovascular cycle for timing of the individual's musculoskeletalactivity (1102). For example, a device, such as, a wearable device(e.g., a wristband), mobile device (e.g., a mobile phone), or computersystem, can provide feedback prompts to the individual. The feedbackprompts are provided with a timing relationship with respect to theindividual's heart's contraction events. When the individual times theirMSK activity to coincide with the prompts favorable MSK pump timing canbe achieved.

A system can be further configured to evaluate an individual's MSKactivity timing relative to the target timing by comparing data from MSKmovement or muscle contraction cycle sensors (e.g., accelerometers,gyroscopes. EMG sensors, magnetic sensors, mechanical sensors, pressuresensors, cameras, radar, or electromagnetic wave based sensors) to thatof CV sensors. Many forms of sensors and ways of mounting sensors to anindividual arc contemplated herein, including but not limited to directskin mounting (e.g., by way of straps, adhesive), or via clothing,jewelry, mobile electronic devices, implants, cardiac pacemakers, and soon.

For activities that utilize stationary or non-stationary equipment(e.g., an exercise treadmill, elliptical, stepper, console gamingsystem, or bicycle), timing of an individual's MSK movements can bedetected with comparable sensors to those mentioned above mounted to orintegral within, or placed nearby, the equipment (e.g., accelerometerbased, gyroscopic, magnetic, hall-effect, optical, magneto resistive,inductive, capacitive, rpm sensors, etc.). In order to guide the timingof the user's activity, prompts can be delivered to the individual viaone or more of an auditory, visual, tactile, electrical, or otherappropriate recognizable cue.

Some embodiments provide additional guidance to lead an individual to aspecific cadence or a specific HR during rhythmic physical activities.For example, a system may use an audible feedback prompt to guide anindividual for maintaining MCP during running. The acousticcharacteristics (e.g., pitch) of the prompt can be adjusted to assistthe individual. For example, the pitch of each prompt, or the pitch ofone prompt in 2 or one prompt in 4, etc., can indicate the user'scurrent HR or cadence relative to the desired HR or cadence so that theuser can adjust their activity accordingly.

More specifically, a user's target HR and cadence can beset at, forexample, a rate and range of 180+/−2 beats and steps per minute. Whenthe user's HR is 175 beats per minute (below the target range), then thepitch of each nth prompt (e.g., each 4^(th) prompt) could be lower thanthe pitch of the other 3 prompts to indicate that the HR is too low.Varying the pitch in this manner notifies the individual to increasetheir workload or effort in order to increase their HR and cadence (whenstep rate and HR are synchronized) towards the target level. An increasein work or effort can be achieved in different ways, depending on theuse case. For example, in a timed run, under steady state runningconditions, a longer stride length increases work output at a givencadence. In a run at a set speed (e.g. when a runner wants to remain atthe speed other runner), then the work output can be increased toincrease HR by other maneuvers, such as raising the knees higher witheach step, or pushing higher off the ground in a more bounding step, ortensing more muscle groups with each step, or by adding isometric upperextremity contractions with each step, etc. One's ability to increasework output at a given cadence and speed may also be facilitated by theuse of ambulatory exercise equipment, such as hand grip or arm or legbased motion resisting exercise devices. When the target HR is achieved,the pitch of each 4th prompt could return to same pitch as the other 3prompts in each 4-prompt cycle. Alternatively, if the HR gets to beabove the target range, the user could be notified by each 4th promptbeing higher in pitch than the other 3 baseline prompts in each 4-promptcycle. Varying the pitch in this manner notifies the individual todecrease the work or effort in order to decrease the user's HR andcadence to the target level. Other acoustic characteristics couldalternatively be used (e.g., timbre, volume, duration, etc.) for audibleprompts.

A wide variety of other indicators can be similarly utilized. Examplesinclude, but are not limited to: other forms of audible prompts (e.g., avoice prompt, recorded or synthesized, indicating a desired increase ordecrease in pace), a visual prompt (e.g., green for increase pace, redfor decrease pace), a tactile prompt (such as a vibration or series ofvibrations indicating a desired increase or decrease in pace), or acombination of two or more of such audible, visual, and tactile prompts.

In other embodiments, visual feedback is provided to the user toindicate the HR and/or cadence relative to one another and/or relativeto a target value or target range. The indication of the real-time HRand movement cadence and relationship relative to each other, providesinsight into how an individual can actively bring the CV and MSK pumpingcycles into alignment at a chosen or provided target parameter (e.g. ata desired effort, speed, cadence, HR, etc.).

In some embodiments, visual feedback is provided to the user to indicatethe HR and/or cadence relative to one another +/− relative to a targetvalue or target range. This indication of their real-time HR andmovement cadence and relationship relative to each other, providesinsight into how the user can actively bring the CV and MSK pumpingcycles into alignment at a chosen or provided target parameter (e.g. ata desired effort, speed, cadence, HR, etc.). As example user interfacesillustrate in FIGS. 12 and 13, when the HR and cadence are not equal,purposefully altering one or both can be leveraged to bring the HR andcadence into alignment, i.e. (1) alter cadence towards a target HR,and/or (2) alter work output (e.g. speed, stride length, effort, etc.)to effect HR changes towards a target cadence. If desired, informationcan be provided on the real-time relationship of both HR and cadencerelative to a target value or target range.

FIGS. 12A, 12B, and 12C illustrate example user interface screens ofvisual user prompts in the form of real-time graphical representations.FIGS. 12A, 12B, and 12C depict needles 1201 and 1202 on gauge 1206.Needles 1201 and 1202 represent rates of cadence 1203 (e.g., anindividual's cadence during rhythmic MSK activity) and HR 1204 (e.g.,the individual's HR during the rhythmic activity) respectively relativeto one another. For the individual to achieve favorable hemodynamics,for example, MCP, needles 1201 and 1202 are to overlap (equivalently, bein alignment).

FIG. 12A depicts cadence 1203 at a lower rate than HR 1204 (i.e., thatrate indicated by needle 1201 is lower rate than the rate indicated byneedle 1202 on gauge 1206). Under the circumstances in FIG. 12A, theindividual is being visually prompted to alter one or both of cadence1203 and HR 1204 to bring cadence 1203 and HR 1204 (and associatedneedles 1201 and 1202) into alignment. That is, the individual isprompted to alter cadence 1203 towards a target heart rate, and/or (2)alter work output to effect changes to HR 1204 towards a target cadence.FIG. 12B depicts cadence 1203 still at a lower rate than, but closer to,HR 1204 (i.e., relative to FIG. 12A, the rate indicated by needle 1201is lower than, but closer to, the rate indicated by needle 1202 on gauge1206). Under the circumstances in FIG. 12B, the individual is stillbeing visually prompted to alter one or both of cadence 1203 and heartrate 1204 for alignment. FIG. 12C depicts cadence 1203 and HR 1204 inalignment (i.e., needles 1201 and 1202 are in alignment). Under thecircumstances in FIG. 12C, the individual is being visually prompted tomaintain cadence 1203 and HR 1204 (since maintaining more favorablehemodynamics is possibly when cadence 1203 and HR 1204 are generallyaligned).

When overlapped, overlapping needles can be differentiated from oneanother through a variety of means, including color, shape, texture orsize change in the needles when they are separated and as they overlap.In one embodiment, needle 1201 is blue, needle 1202 is red, and whenneedles 1201 and 1202 overlap, the overlapping needles are shown inpurple. A graphical representation can also indicate the current HR andcadence values relative to a target HR and target cadence value or zoneof values. For example, a shaded triangular target zone 1207 can beadded on gauge 1206 from HR & cadence 155 to 165 could be added in orderto represent an exemplary target HR and cadence zone (shown in FIG.12C).

As such, visual feedback can provide significant information to anindividual about what needs to be done in order to ensure favorablehemodynamics (e.g., achieve MCP) at equivalent HR and cadence values.For example, if the individual can see that the HR is below the cadence,then the HR needs to be increased (work output needs to be increased)or/and the cadence needs to be decreased, and vice-versa. Alternatively,if the individual can see that the HR is noted to be below target zone1207, work output needs to be increased to increase the HR towards thetarget. In yet another example, if the user can see that the cadence isabove target zone 1207, but the HR is below target zone 1207, work needsto be increased to raise the HR, while the cadence needs to bedecreased. In order to increase work output and HR while simultaneouslylowering cadence while running on a flat surface, a user could increaserunning speed through an increase in stride length that is adequate toenable an overall decrease in cadence. In exemplary embodiments of agraphical interface, an individual can be reminded or directed toincrease or decrease their stride length through audible or writtenwords or symbols or other readily identifiable means of providingbiofeedback to the user.

FIGS. 13A and 13B illustrate other example user interface screens ofvisual user prompts provided as a graphic. FIGS. 13A and 13B depict therelative rates and timing of the MSK and CV events and indicate therespective pumps' coordination. The ongoing real-time user average HRvalue is shown numerically in FIG. 13A by 1302, and average cadence by1301. The user's HR and cadence are further shown graphically by shaded(alternatively, colored) circles 1305 and 1304, respectively, bothlocated along arc 1303 that is scaled from 60 (1309) to 220 (1310) perminute. In this instance, the displayed average HR 1302 is greater thanthe average cadence 1301, thus the two shaded circles depict the 10/mindifference in their numeric values 1302 and 1301. Also shown is shadedarea 1306, indicating a target average HR and cadence band centered on atarget rate value of 150 per minute (1307). The user is thus presentedwith a graphical indication that their cadence 1304 and HR 1305 do notmatch, nor does either value match the pre-defined target range shown inshaded area 1306.

FIG. 13B shows the user's sensed characteristics a short time later (perelapsed time values 1312 and 1313, shown in M:SS.s), after the user'saverage cadence increased to 132/min (1311), a value that now matchesthe average HR 1302. The graphical depiction of cadence 1304 nowoverlays HR 1305, as both rates share a common value. The relativetiming of the MSK and CV pumps (equivalently, “phase relationship”between the MSK and CV pumps) is indicated as a value of “35” (1314), inthis example using units of percent of the RR interval (% RRI), anddepicted graphically as points 1315 that follow along a circular scale1316 that spans 0-100%. Points 1315 also indicate that the MSK eventsare occurring at approximately 35% of the RR-interval at the time ofthis observation. In an alternative embodiment, one or both of thenumeric timing value 1314 and graphic depiction 1315, 1316 may beeliminated.

While the example graphic interfaces shown in FIGS. 12 and 13 depict thecurrent HR and cadence values graphically in a polar plot with needlesor both located along an arc, other depictions may be used withoutdeparting from the concepts described herein. For example, the data maybe presented along alternative piecewise linear and/or curvilinearprofiles such as a line, ellipse, trapezoid, etc., or in side-by-sidedepictions for the various measures located along their own profile orset of axes. And while the figures are shown in gray-scale, colorgraphics may also be used.

Embodiments of the invention can be used to train individuals to achieveand experience the physical sensation of MCP. For example, the systemcan prompt an individual to move with and maintain a target timing, thenslowly decrease the magnitude of the prompt when the system determinesthat accuracy of MSK pump timing relative to the target timing has beenachieved and maintained for a set amount of time (e.g., some number ofseconds, minutes, etc.). The prompt magnitude returns to its initiallevel if and when the accuracy of MSK pump timing relative to targettiming diminishes (e.g., outside of some threshold).

Decreasing prompt magnitude can include decreasing the volume an audioprompt at a specified rate (while accuracy is maintained) until theprompt eventually become inaudible. The audio prompt can again becomelouder if and when accuracy diminishes. Decreasing prompt magnitude canalso include decreasing the recurrence of presenting an audio prompt ata specified rate (while accuracy is maintained). The recurrence ofpresenting the audio prompt can increase if and when accuracydiminishes. For example, when an individual is running, a prompt couldreversibly change from every step to every other step to every 4th stepas accuracy is maintained for specified durations of time. Throughpractice, an individual can become increasingly capable of maintainingfavorable hemodynamics (e.g., MCP) with reduced prompting. Eventually,the individual may be able to maintain favorable hemodynamics (e.g. MCP)independent of any prompts. Similar mechanisms can be used withvirtually any type of prompt, including visual, tactile, electrical, orother appropriate recognizable cues.

FIG. 14 illustrates a flow chart of an example method 1400 for changingprompt magnitudes to guide a user to obtain favorable coordination oftiming between MSK and cardiovascular pumping. Method 1400 includessensing MSK timing (or equivalently phase) relationship relative tocardiovascular timing (1401). For example, a processor can processsignals from one or more motion sensors and from one or more heartsensors (e.g., ECG, PPG, etc.) attached to an individual. From theprocessing, the processor can determine MSK pump timing relative to CVpump timing for the individual. Method 1400 includes determining if therelationship between musculoskeletal pump timing and cardiovascular pumptiming has been favorably coordinated for a specified duration (decisionblock 1402). For example, the processor can determine if MSK pump timingrelative to CV pump timing has been favorably coordinated for anindividual for a specified period of time (e.g., some number of seconds,minutes, etc.). Favorably coordinated can include substantiallyremaining within a target relative timing range within a specifiedstatistical measure (e.g., a defined standard deviation) of a targettiming relationship or target timing relationship range. When MSK pumptiming relative to CV pump timing has been favorably coordinated for thespecific duration (YES at decision block 1402), method 1400 includesdecreasing prompt magnitude (1403). For example, the processor candecrease the volume, brightness, frequency of presentation, etc. of aprompt. When MSK pump timing relative to CV pump timing has not beenfavorably coordinated for the specific duration (YES at decision block1402), method 1400 includes maintaining or increasing the promptmagnitude (1404), up to a maximum that may be set by the user. Forexample, the processor can maintain or increase the volume, brightness,frequency of presentation, etc. of a prompt.

Method 1400 includes providing a musculoskeletal timing feedback prompt(1405). For example, a processor can provide a musculoskeletal timingfeedback prompt in accordance with a decreased, maintained, or increasedmagnitude as appropriate. Appropriate can include within a range ofmagnitudes.

In alternative embodiments, prompts can be turned on or off as opposedto deceased or increased. A mode providing a simple on/off selection maybe selected for providing or not providing a prompt during activity.

In some embodiments, auditory MSK target timing prompts are providedthrough music, with the beat of the music providing the target timing.The volume of the prompt beat can be increased or decreased relative tothe rest of the music by the user. Alternately, the volume of the promptbeat relative to the rest of the music can be programmed toautomatically increase and decrease, depending on the user's ability toinitiate MSK pump activity with timing that is consistent relative tothe prompt timing.

FIG. 15 illustrates an example of a wrist worn device 1501 that guidesan individual to optimize the timing of rhythmic musculoskeletalactivity. By optimizing the timing of rhythmic musculoskeletal activity,the individual can achieve favorable hemodynamics, including MCP. Wristworn device 1501 includes dual volume controls 1502 and 1503. Volumecontrol 1502 controls volume for the beat of the music (e.g. base, drum,metronome, etc.) and volume control 1503 controls volume for the musicwith its normal beat volume. Dual volume controls can be useful whenlearning to move to a musical beat accurately, or with certain musicwherein the beat of the music is less easy to discern.

Further embodiments can provide an additional prompt to an individualfor timing respiration. In these further embodiments, an individual iscoached to inspire or to expire with prompts similar to those used forMSK pump timing. For example, every prompt may be used for step timingwhen running, while the user is instructed to begin inspiration withevery 4^(th) prompt. As such, every 4^(th) prompt may be provided with adifferent pitch than the other three prompts. In another embodiment, thevolume of a breathing prompt may differ from the other prompts. In otherexamples, a breathing prompt with a different acoustic characteristicfrom the MSK activity prompts can be provided so that the user timesinspiration or expiration to every 2^(nd), 3^(rd), 5^(th) 6^(th) or7^(th) step, for example.

When audible characteristics of intermittent repository prompts differfrom the audible characteristics of the prompts for MSK activity, theintermittent respiratory prompts can be configured to confer additionalinformation to an individual beyond MSK activity and respiratory timing.For example, differing the pitch, duration, and volume between theintermittent and regular prompts can enable a user to distinguish amongthem. For example, if breathing prompts and an individual's target MSKactivity timing arc both desired, the differing pitch of the breathingprompt can be provided at three levels, for example, low, medium, andhigh frequency pitches (all differing from the stepping pitch or othercharacteristic). Each differing pitch prompt indicates when to breathe,while the lowest pitch indicates that the HR is below a target; a mediumpitch indicates the HR is within the target range; and a high pitch thatthe HR is above the target rate. In another example, the audibleprompts' timbre could vary in addition to or instead of varying pitch.

The training process (for MSK activity and/or respiration) can beprovided in the form of a game or games. In one example, the first“level” of the game is the recording of baseline MSK pumping activity,without a prompt, but with consistency of MSK pump timing rewarded. Oncethat level has been completed, a higher level can include steppingaccurately to a simple prompt's timing. Another higher level can includestepping accurately to a more complex prompt, such as one providedwithin more and more complex music as the game advances. Other optionallevels include training the user and rewarding the user for accurate MSKpump timing in response to other audible, or non-audible (e.g. visual ortactile) prompts. Additional challenges in the game can includeincreasing the complexity of the prompted MSK activity, including a widevariety of movements or physical tasks such as walking, stomping,jumping, skipping, turning, dancing or engaging in any of an extremelywide variety of movements. Still other optional levels reward a user forcontinuing to maintain accurate MSK pump timing relative tocardiovascular pump timing even with the prompt no longer available tothe user.

In further example embodiments of a gaming challenge, the longer theuser can maintain accurate timing without or after withdrawal of anaudible or visible or tactile prompt, the better the score in the game.In yet further examples, the magnitude of an MCP effect can be monitoredand rewarded, for example, through the achievement of target changes inHR, tissue perfusion, respiration. BP, or blood flow, volume or pressurewaves monitored by ECG, PPG, or captured in video images or other easilyaccessible means of physiological monitoring.

Mechanisms for providing auditory, visual, or tactile prompts to guide aindividual to achieve target step timing can also be integrated withother (e.g., existing) games to enable the individual achieve favorablehemodynamics (e.g., MCP) during play. Games can leverage a variety ofsensors in order to accurately characterize an individual'smusculoskeletal activity and timing relative to their CC timing.Different types of MSK activity can be used to trigger, in real-time, atleast one of musical notes, chords, visual feedback, and tactilesensations, while the cardiac cycle and/or respiratory cycle may triggeradditional musical beats, tactile sensations, or visual feedback,guiding a user to achieve MCP through the creation of pleasant musicalrhythms and sounds.

Embodiments can work with exercise gaming systems, exercise machines, orheads-up audiovisual displays. Several popular commercial games,including Dance Dance Revolution, Guitar Hero, and Tap Tap Revenge haveencouraged users to move different parts of their body in time with anaudio prompt. In these commercial examples, the movement prompt is timedto correspond to the beat or notes of a specific music composition.

FIGS. 16A, 16B, and 16C illustrate example paired left and right footstep sequences 1601, 1602, and 1603 that can be presented to anindividual when playing a game. Steps sequences 1601, 1602, and 1603 canprovide feedback as to the accuracy of an individual's MSK activitytiming in a fashion that provides visual cues as to what movements willbe expected in the future (step sequences 1602 and 1603) as well as tothe accuracy of the movement timing relative to the target timing (stepsequence 1603). As illustrated in FIG. 16C, advanced levels of the gamemay encourage the user to step with a timing that encourages MCP butwith a step sequence that includes hopping on one foot, etc. Embodimentsof this type of game may leverage one or more foot-strike sensors ineach shoe, foot-strike sensors in a gaming pad or deck on the floor, orvideo cameras in order to more accurately gauge the user's movement andmovement timing. Further embodiments provide guidance to the user tomove the foot or other parts of the body in different ways (e.g. step toside, slide foot, forefoot strike, tap heel, etc.) and leverage themultiple foot sensors in different parts of the shoe, or other movementsensors located elsewhere, to provide feedback as to the accuracy ofthose movements vs. the prompted movements.

Exercise Stress Tests

Embodiments of the invention can also be used to reduce false positivesduring exercise stress tests. Exercise stress tests are used to diagnoseheart disease but can suffer from false positives leading tounnecessary, expensive, invasive, and risky studies and treatments. Forexample, stepping consistently during cardiac systole may create atemporary increase in cardiac afterload, systolic blood pressure, and HRalong with a simultaneous decrease of arterial and venous blood supplyto heart, even in an absence of heart disease—potentially causing ECG,ultrasound, or other monitored cardiovascular changes that can appearsimilar to those changes known to occur in the presence of diseased(obstructed) coronary arteries. Additionally, during a treadmillexercise stress test, leads are usually attached on skin and softtissue, largely across the anterior and lateral torso of the patient.Thus, as the patient subsequently walks or runs on the treadmill track,the position of the leads will bounce up and down, to a degree thatcorrelates with the stability of the soft tissue directly under the skinelectrodes, repeatedly changing the position of many of these electrodesrelative the position of the heart with each foot strike.

Changing these relative positions changes the measured electricalvectors in a predictable manner. As a result, stepping consistently atthe same time in the heart cycle (HR=MSK cadence) can lead to motionartifacts that create a stable but distorted ECG tracing. Some of thesecommon motion artifacts can cause false positive stress tests. When softtissue under the chest leads is voluminous or highly mobile, as may be amore common occurrence with women than men, the larger the likelihoodand magnitude of the potential movement artifact and resultant falsepositive incidence.

Accordingly, the timing of rhythmic physical activity relative to amonitored ECG can be further analyzed during an exercise stress test.The analysis can expose ECG changes potentially (or likely) to berelated to effects of inverse iMCP (as opposed to some other cardiaccondition, such as, coronary artery disease) on cardiac stress andperfusion. The analysis can also identify ECG changes that are likely tobe due to motion artifacts resulting from rhythmic step timing at aconsistent timing relative to the heart's cycle (and that mightotherwise be indicated as a false positive for a cardiac condition, suchas, heart disease).

In an additional example, a stress test system can includes separatemovement monitors (e.g. accelerometers) on multiple leads, includingmovement monitors anchored to portions of the body that are less likelyto move separately from the heart (e.g., a lead and accelerometer oraccelerometer alone placed on the skin on top of the shoulder would beless likely to have the same movement artifact as a precordial lead oversoft tissue on the chest wall). These separate MSK activity monitors canmeasure any difference in movement between the leads over soft tissueand the leads moving consistently with the heart, and can be analyzed toautomatically identify or eliminate the movement artifact in the ECGtracing.

FIG. 17 illustrates a flow chart of an example method 1700 for useduring an exercise stress test to reduce false positives. Method 1700includes sensing a patient's cadence (1701). For example, a processorcan receive signals from one or more (e.g., activity or other described)sensors implanted in and/or externally attached to the patient, orincorporated in, attached to, or placed on the exercise equipment, orset at a distance from the patient (e.g., video camera, radar, etc.).From the signals, the processor can determine the patient's cadence.Method 1700 includes sensing the patient's HR (1702). For example, aprocessor can receive signals from one or more heart sensors implantedin and/or externally attached to the patient. From the signals, theprocessor can determine the patient's HR.

Method 1700 includes determining the difference between the patient'scadence and the patient's HR (1703). For example, the processor candetermine the difference between the patient's cadence and the patient'sHR. Method 1700 includes determining if the patient's cadence and thepatient's HR are sufficiently similar (decision block 1704). Forexample, the processor can determine if the patient's cadence and thepatient's HR are sufficiently similar. When the patient's cadence andthe patient's HR are not sufficiently similar (No at decision block1704), method 1700 returns to 1701. That is, the patient's cadence andHR are sufficiently different, with little, if any, of the describedconsistent motion artifact-induced distortions present in an averagedECG signal, and little, if any, consistent iMCP induced cardiac stress,therefore suggesting that any detected ECG changes of concern at thattime are less likely to be false positives.

When the patient's cadence and the patient's heart rate are sufficientlysimilar (Yes at decision block 1704), and resulting movement artifactsare potentially distorting an averaged ECG signal, or, depending on therelative MSK pump timing and CV pump timing, potentially lead to ECGchanges induced by iMCP, method 1700 includes one or more of: changingtreadmill track speed, changing treadmill incline, annotating an ECGreport to indicate a potential artifact or episode of iMCP, alerting thetest administrator (e.g. visual or auditory cue to change treadmillsettings or direct a change in the patient's activity), and providing apatient with a cadence prompt to guide them in stepping with a targetedcadence, or timing, relative to cardiac cycle (1705). For example, theprocessor (or the test administrator) can change treadmill track speedor incline, provide any of the described prompts to the patient, orannotate an ECG report for the patient. Changing treadmill track speedand/or providing prompts are remedial measures to assist the patient instepping at a rate that differs from their HR so as to neither causeconsistent distortion to their ECG signals nor cause ECG changes inducedby persistent iMCP. Annotating an ECG report can enable a healthcareprovider and patient to avert a possible false positive stress test. Themovement artifacts may be more likely to occur in certain leads due tothe axis of the heart in the individual being tested (axis as usedherein means position of the heart in the chest, which can differbetween individuals). Analysis of the axis is used by algorithms inembodiments of this system and method in order to more specificallyidentify and annotate or even potentially modify the ECG tracing inorder to correct for identified movement artifacts, particularly thoseartifacts that are most likely to lead to the false conclusion thatmyocardial ischemia is present.

In alternative embodiments of an exercise stress test system and method,a healthcare provider may improve the sensitivity of a stress test bypurposefully inducing iMCP. Guiding a user to “Step to the beat” with ahemodynamically unfavorable timing (e.g. foot strike during systole), orprogramming a pacemaker to “beat to the step” with a timing that inducesiMCP, increases stress on a heart in a controlled environment byincreasing myocardial work (HR & systolic blood pressure) whiledecreasing myocardial perfusion pressure. Because iMCP can be anaturally occurring phenomenon, a healthcare provider may find it usefulto stress the heart in this fashion. One example of where this type of“extra stress” might be useful might be in testing individuals who areregularly subject to potentially dangerous or high physical stress orhigh risk environments, for example pilots, “at risk” athletes (e.g.with known CV conduction, structural heart, or genetic defects),firefighters, soldiers, air traffic control personnel or high levelsecurity workers. Another potential use case may be the testing ofindividuals who exhibit probable or possible symptoms of CV disease(e.g. angina, palpitations, syncope) during activities of daily livingor normal exercise, yet show no evidence of CV disease after a standardcardiovascular medical workup. Further embodiments can include stresstest protocols that compare the patient's ECG during MCP to the ECGduring iMCP for further diagnostic or prognostic benefit.

Throughout the description and following claims, it should be understoodthat where values of HR and cadence are used, the equivalentfunctionality can be obtained by alternatively using R-to-R period andMSK-event-to-MSK-event periods, as each are related through theirrespective mathematical inverses (e.g., HR=1/RRI). Furthermore, wheredelay timing between MSK and CC events may be computed using time-domainmethods to determine their relative timing, equivalent functionality canbe achieved with methods that use the signals in their entirety, such asfrequency-domain and its accompanying phase-domain computations (e.g.Fourier transforms), cross-correlation computations, and other suchmethods.

FIG. 18 illustrates an example block diagram of a computing device 1800.Computing device 1800 can be used to perform various procedures, such asthose discussed herein. Computing device 1800 can function as a server,a client, or any other computing entity. Computing device 1800 canperform various communication and data transfer functions as describedherein and can execute one or more application programs, such as theapplication programs described herein. Computing device 1800 can be anyof a wide variety of computing devices, such as a mobile telephone orother mobile device, a desktop computer, a notebook computer, a servercomputer, a handheld computer, tablet computer and the like.

Computing device 1800 includes one or more processor(s) 1802, one ormore memory device(s) 1804, one or more interface(s) 1806, one or moremass storage device(s) 108, one or more Input/Output (I/O) device(s)1810, and a display device 1830 all of which are coupled to a bus 1812.Processor(s) 1802 include one or more processors or controllers thatexecute instructions stored in memory device(s) 1804 and/or mass storagedevice(s) 1808. Processor(s) 1802 may also include various types ofcomputer storage media, such as cache memory.

Memory device(s) 1804 include various computer storage media, such asvolatile memory (e.g., random access memory (RAM) 1814) and/ornonvolatile memory (e.g., read-only memory (ROM) 1816). Memory device(s)1804 may also include rewritable ROM, such as Flash memory.

Mass storage device(s) 1808 include various computer storage media, suchas magnetic tapes, magnetic disks, optical disks, solid state memory(e.g., Flash memory), and so forth. As depicted in FIG. 18, a particularmass storage device is a hard disk drive 1824. Various drives may alsobe included in mass storage device(s) 1808 to enable reading from and/orwriting to the various computer readable media. Mass storage device(s)1808 include removable media 1826 and/or non-removable media.

I/O device(s) 1810 include various devices that allow data and/or otherinformation to be input to or retrieved from computing device 1800.Example I/O device(s) 110 include cursor control devices, keyboards,keypads, barcode scanners, microphones, monitors or other displaydevices, speakers, printers, network interface cards, modems, cameras,lenses, CCDs or other image capture devices, and the like.

Display device 1830 includes any type of device capable of displayinginformation to one or more users of computing device 1800. Examples ofdisplay device 1830 include a monitor, display terminal, videoprojection device, and the like.

Interface(s) 1806 include various interfaces that allow computing device1800 to interact with other systems, devices, or computing environmentsas well as humans. Example interface(s) 1806 can include any number ofdifferent network interfaces 1820, such as interfaces to personal areanetworks (PANs), local area networks (LANs), wide area networks (WANs),wireless networks (e.g., near field communication (NFC), Bluetooth,Wi-Fi, etc., networks), and the Internet. Other interfaces include userinterface 118 and peripheral device interface 1822.

Bus 1812 allows processor(s) 1802, memory device(s) 1804, interface(s)1806, mass storage device(s) 1808, and I/O device(s) 1810 to communicatewith one another, as well as other devices or components coupled to bus1812. Bus 1812 represents one or more of several types of busstructures, such as a system bus, PCI bus, IEEE 1394 bus, USB bus, andso forth.

Although the components and modules illustrated herein are shown anddescribed in a particular arrangement, the arrangement of components andmodules may be altered to process data in a different manner. In otherembodiments, one or more additional components or modules may be addedto the described systems, and one or more components or modules may beremoved from the described systems. Alternate embodiments may combinetwo or more of the described components or modules into a singlecomponent or module.

The foregoing description has been presented for the purposes ofillustration and description. It is not intended to be exhaustive or tolimit the invention to the precise form disclosed. Many modificationsand variations are possible in light of the above teaching. Further, itshould be noted that any or all of the aforementioned alternateembodiments may be used in any combination desired to form additionalhybrid embodiments of the invention.

Further, although specific embodiments of the invention have beendescribed and illustrated, the invention is not to be limited to thespecific forms or arrangements of parts so described and illustrated.The scope of the invention is to be defined by the claims appendedhereto, any future claims submitted here and in different applications,and their equivalents.

1-5. (canceled)
 6. A method of determining a timing of a heart pacingsignal using a respiratory timing of the individual, the methodperformed by an implantable processor and comprising: receiving signalsfrom at least one respiratory sensor positioned in or on the individual;determining from the sensor signals a rhythmic musculoskeletal pump rateand a rhythmic musculoskeletal pump timing of the individual;determining a target heart rate range for the individual, relative tothe rhythmic musculoskeletal pump timing; determining whether a currentheart rate is in the target heart range and is an integer multiple ofthe rhythmic musculoskeletal pump rate; and when the current heart rateis in the target heart range and is the integer multiple of the rhythmicmusculoskeletal pump rate, outputting a pacing signal to the heart ofthe individual to pace the heart in the target heart rate range toincrease musculoskeletal counterpulsation from musculoskeletal bloodpumping, thereby providing at least one of: an increase in cardiacpreload or an increase in cardiac stroke volume.
 7. The method of claim6, further comprising receiving second signals from a cardiovascularcycle sensor for detecting a cardiac cycle of a patient; and determiningthe target heart rate range based on the second signals.
 8. The methodof claim 7, further comprising determining the current heart rate of theindividual.
 9. The method of claim 6, further comprising receivingsecond signals from a musculoskeletal activity sensor; and determining astep timing of the individual based on the second signals.
 10. Themethod of claim 9, further comprising outputting a breathing guidance tothe individual to coordinate a breath timing with the step timing of theindividual.
 11. A dynamic pacemaker system for artificially pacing apatient's heart, comprising: a respiratory sensor for detecting arespiratory timing of a patient; an implantable electrical leadconnectable to a heart of the patient; an implantable pulse generatorcoupled to the electrical lead and configured, with the electrical lead,to electrically stimulate the heart in accordance with a pacing signal;and an implantable processor electrically coupled to the respiratorysensor and the pulse generator, wherein the processor is configured toperform a method comprising: receiving signals from the respiratorysensor; determining from the sensor signals a rhythmic musculoskeletalpump rate and a rhythmic musculoskeletal pump timing of the individual;determining a target heart rate range for the patient, relative to therhythmic musculoskeletal pump timing; determining whether a currentheart rate is in the target heart range and is an integer multiple ofthe rhythmic musculoskeletal pump rate; and when the current heart rateis in the target heart range and is the integer multiple of the rhythmicmusculoskeletal pump rate, outputting a pacing signal to the heart ofthe individual to pace the heart in the target heart rate range toincrease musculoskeletal counterpulsation from musculoskeletal bloodpumping, thereby providing at least one of: an increase in cardiacpreload or an increase in cardiac stroke volume.
 12. The dynamicpacemaker system of claim 11, further comprising a cardiovascular cyclesensor for detecting a cardiac cycle of the patient, wherein theprocessor is further configured to receive second signals from thecardiovascular cycle sensor; and determine the target heart rate rangebased on the second signals.
 13. The dynamic pacemaker system of claim12, wherein the processor is further configured to determine the currentheart rate of the individual.
 14. The dynamic pacemaker system of claim12, wherein the cardiovascular cycle sensor comprises one of: anelectrocardiogram, a photoplethysmogram, or an electronic auscultationsensor.
 15. The dynamic pacemaker system of claim 11, further comprisinga musculoskeletal activity sensor, wherein the processor is configuredto receive second signals from the musculoskeletal activity sensor; anddetermine a step timing of the individual based on the second signals.16. The dynamic pacemaker system of claim 15, wherein the processor isconfigured to output a breathing guidance to the individual tocoordinate a breath timing with the step timing of the individual. 17.The dynamic pacemaker system of claim 15, wherein the musculoskeletalactivity sensor comprises one of: a uniaxial accelerometer, a multiaxialaccelerometer, a magnetometer, a gyroscope, a piezoelectric material, ora pressure sensor.
 18. The dynamic pacemaker system of claim 11, whereinthe respiratory sensor is positioned within an artificial pacemakerimplanted in the individual.
 19. The dynamic pacemaker system of claim11, wherein the respiratory sensor is an external wireless sensor.